Wittig reactions chain elongation

Corey s retrosynthetic concept (Scheme 9) is based on two key transformations a cationic cyclization and an intramolecular Diels-Alder (IMDA) reaction. Thus, cationic cychzation of diene 50 would give a precursor 49 for epf-pseudo-pteroxazole (48), which could be converted into 49 via nitration and oxazole formation. Compound 50 would be obtained by deamination of compound 51 and subsequent Wittig chain elongation. A stereocontroUed IMDA reaction of quinone imide 52 would dehver the decaline core of 51. IMDA precursor 52 should be accessible by amide couphng of diene acid 54 and aminophenol 53 followed by oxidative generation of the quinone imide 52 [28]. 

This classification leaves out of account the other applications to a-amino acids (e.g., as chiral auxiliaries). Besides, the approach shown in Scheme 2 excludes higher carbon chain elongation (from C5 up to C16), which can be effectively realized using organo-metallic additions and Wittig-type reactions [e.g., see Ref 17]. 

A solid-phase technique that uses an N-protected u,p-unsaturated y-amino acid proved to be effective for ozonolysis due to its ethylenic functionality. The linker was prepared from the Wittig reaction between (ethoxycarbonylethylene)triphenylphosphorane and either the Boc or Fmoc N-protected a-amino aldehyde. The Boc or Fmoc protecting group was removed and the chain was elongated by standard BOP coupling 49,52 53 61 The peptide-resin was then cleaved by ozonolysis, which afforded the desired aldehyde 49 ... 

Fig. 11. 29. Aldehyde — alkyne chain elongation via [1 -rearrangement of a vinyl carbenoid (Corey-Fuchs procedure). The aldehyde and phosphonium ylide A generated in situ undergo a Wittig reaction and form the 1,1-dibromoalkene. In the second stage, the dibromoalkene is reacted with two equivalents of n-BuLi and the vinyl carbenoid C is formed. The carbenoid undergoes H migration to form the alkyne B. The alkyne B reacts immediately with the second equivalent of w-BuLi to give the lithium acetylide.

The Michael addition represents an extremely efficient synthetic method for achieving chain elongation by adding a three (or more) carbon fragment electrophile to a nucleophilic moiety. Notice that the typical Michael electrophiles (e.g. 90) are products of condensation of carbonyl compounds and can be easily formed via the aldol-like condensation, the Wittig reaction (with ylides like 81), the Perkin reaction, or the Mannich reaction (see below). 

SCHEME 6.65 The Wittig reaction is useful for the chain elongation of sugars at the reducing end. 

In another report, paromamine 92 was converted to the pseudodisaccharide 100, which is a constituent of the structure of oxyapramycin 101 (compounds 100, 101). Two-carbon chain elongation was performed by Wittig reaction on a 5 -aldehyde derivative followed by osmium tetraoxide hydroxylation, which after lactonization in the basic condition, followed by reduction and deprotection, afforded compound 100 [61]. 

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